To determine the effects of the non-classic psychedelic, ibogaine, on cognitive functioning. Ibogaine is an indole alkaloid derived from the Tabernanthe Iboga plant family, indigenous to Africa, and traditionally used in spiritual and healing ceremonies. Ibogaine has primarily been studied with respect to its clinical efficacy in reducing substance addiction. There are, however, indications that it also may enhance recovery from traumatic experiences. Ibogaine is a Schedule 1 substance in the USA.

Participants were U.S. Special Operations Veterans who had independently and voluntarily referred themselves for an ibogaine retreat at a specialized clinic outside the USA prior to learning about this observational study. After meeting rigorous screening requirements, 30 participants were enrolled, all endorsing histories of combat and repeated blast exposure, as well as traumatic brain injury. Participants were seen in person pre-treatment, post-treatment, and one-month post-treatment for neuropsychological testing, neuroimaging, and collection of clinical outcome measures. All 30 participants were seen pre- and post-treatment, of whom 27 were also able to return one-month post-treatment.

The neuropsychological battery included the the Hopkins Verbal Learning Test (HVLT), the Brief Visuospatial Memory Test - Revised (BVMT-R), the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Working Memory Index (Digit Span and Arithmetic) and Processing Speed Index (Symbol Search and Coding), and the Delis-Kaplan Executive Function System (D-KEFS) tests of Verbal Fluency (VF), Trail Making (TMT), Color Word (CW), and Tower Test (TT). For repeated measures, alternate forms were used whenever possible.

Repeated-measures ANOVA revealed significant effects of time, with post-treatment improvements across multiple measures including processing speed (WAIS-IV PSI; F(2,25) = 26.957, p < .001), executive functions (CW Conditions 3 and 4: F(1.445,25) = 11.383, p < .001 and F(1.381,25) = 7.687, p = .004, respectively), verbal fluency (VF Condition 3 correct and accuracy: F(2,25) = 6.419, p = .003 and F(2,25) = 153.076, p < .001, respectively), and verbal learning (HVLT Total Recall (alternate forms used at each time point): F(1.563,23) = 6.958, p = .004). Score progression graphs are presented. Performance on all other cognitive measures did not significantly change following treatment.

To our knowledge, this is the first prospective study examining neuropsychological test performance following ibogaine use at post-treatment and one-month post-treatment time points. Our results indicated that several cognitive domains improved either post-treatment or one-month post-ibogaine treatment, suggesting ibogaine’s therapeutic potential for cognition in the context of traumatic brain injury and mood disorders. Potential explanations include neuroplastic changes, reduction of PTSD and mood-related effects on cognitive functioning, and practice effects. While we found no evidence of negative cognitive consequences for up to one-month post-single-ibogaine treatment, further study of this substance is necessary to clarify its clinical utility and safety parameters.